Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity.

Epidemiological and clinical reports indicate that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we perform cytokine and multiplex immune profiling in COVID-19 patients. We show that hypercytokinemia in COVID-19 differs from the interferon-gamma-driven cytokine storm in macrophage activation syndrome, and is more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels paired with deep-immune profiling shows that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Antigen presenting machinery expression is also reduced in critical disease. Furthermore, we report that neutrophils contribute to disease severity and local tissue damage by amplification of hypercytokinemia and the formation of neutrophil extracellular traps. Together our findings suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.

High dimensional profiling identifies specific immune types along the recovery trajectories of critically ill COVID19 patients.

The COVID-19 pandemic poses a major burden on healthcare and economic systems across the globe. Even though a majority of the population develops only minor symptoms upon SARS-CoV-2 infection, a significant number are hospitalized at intensive care units (ICU) requiring critical care. While insights into the early stages of the disease are rapidly expanding, the dynamic immunological processes occurring in critically ill patients throughout their recovery at ICU are far less understood. Here, we have analysed whole blood samples serially collected from 40 surviving COVID-19 patients throughout their recovery in ICU using high-dimensional cytometry by time-of-flight (CyTOF) and cytokine multiplexing. Based on the neutrophil-to-lymphocyte ratio (NLR), we defined four sequential immunotypes during recovery that correlated to various clinical parameters, including the level of respiratory support at concomitant sampling times. We identified classical monocytes as the first immune cell type to recover by restoration of HLA-DR-positivity and the reduction of immunosuppressive CD163 + monocytes, followed by the recovery of CD8 + and CD4 + T cell and non-classical monocyte populations. The identified immunotypes also correlated to aberrant cytokine and acute-phase reactant levels. Finally, integrative analysis of cytokines and immune cell profiles showed a shift from an initially dysregulated immune response to a more coordinated immunogenic interplay, highlighting the importance of longitudinal sampling to understand the pathophysiology underlying recovery from severe COVID-19.

El delirio como metáfora psicopatológica / Delusion as psychopathological metaphor

La equivocidad que posee el término delirio ha hecho que haya sido considerado un mero artefacto. En este trabajo se pretende considerar su significado como una metáfora psicopatológica para poder pensar las relaciones del hombre con la realidad distorsionadas. Para ello es menester comprender adecuadamente el significado del concepto de hombre y, desde ahí, observar las relaciones que el hombre establece con la realidad. Esta relación siempre es una pretensión de verdad, aunque no exclusivamente judicativa como se la entiende de forma habitual. Desde ese momento, una serie de fenómenos psicopatológicos aparentemente inconexos y extraños entre sí se pueden articular en vista de esa relación esencial veritativa. Dicha relación ha sido sometida a serias y profundas consideraciones filosóficas a lo largo del siglo XX, y no ha dejado de ofrecer su impronta en el concepto psicopatológico de delirio. Esa equivocidad del delirio, finalmente dependiente de una psicopatología que se entiende respecto a una idea de hombre insatisfactoria, puede ser aclarada en función de una mejor y más depurada práctica psicopatológica puesta al día, en lo que respecta a su idea de subjetividad y verdad

The equivocity of the term delusion has led to it being considered a mere artifact. In this study, its meaning is considered as a psychopathological metaphor to be able to consider the relationships of man with the distorted reality. To do so, the meaning of the concept of man must be adequately understood, and based on this, observe the relationships that man establishes with reality. This relationship is always an aspiration to truth, although not exclusively as judicative as is usually understood. From this time, a series of apparently unconnected and rare psychopathological phenomena can be joined in view of the essentially veritative relationship. This relationship has been subjected to serious and deep philosophical considerations during the XX century and has left its mark on the psychopathological concept of delusion. This equivocity of delusion, finally dependent on a psychopathology that is understood in regards to an unsatisfactory idea of man, may be explained based on a better and more purified psycholopathological practice that is up-dated in regards to concepts of subjectivity and truth

Delusion as psychopathological metaphor.

The equivocity of the term delusion has led to it being considered a mere artifact. In this study, its meaning is considered as a psychopathological metaphor to be able to consider the relationships of man with the distorted reality. To do so, the meaning of the concept of man must be adequately understood, and based on this, observe the relationships that man establishes with reality. This relationship is always an aspiration to truth, although not exclusively as judicative as is usually understood. From this time, a series of apparently unconnected and rare psychopathological phenomena can be joined in view of the essentially veritative relationship. This relationship has been subjected to serious and deep philosophical considerations during the XX century and has left its mark on the psychopathological concept of delusion. This equivocity of delusion, finally dependent on a psychopathology that is understood in regards to an unsatisfactory idea of man, may be explained based on a better and more purified psycholopathological practice that is up-dated in regards to concepts of subjectivity and truth.

Evaluación neuropsicológica y déficit en teoría de la mente: estudio comparativo preliminar entre esquizofrenia y síndrome de Asperger / Neuropsycological assessment and deficit within of mind: preliminary comparison between schizophrenia and Asperger,s syndrome

INTRODUCCIÓN: Los pacientes con trastornos generalizados del desarrollo y con esquizofrenia se han relacionado mediante un déficit en la teoría de la mente. El objetivo del presente estudio es comparar el déficit en la realización de tareas de la teoría de la mente entre ambos y su posible relación con los déficit neuropsicológicos. PACIENTES Y MÉTODO: Participan en el estudio 30 sujetos adultos (trastornos generalizados del desarrollo, esquizofrénicos y con trastorno afectivo bipolar, según los criterios del DSM-IV y el CIE-10), explorados mediante tareas de la teoría de la mente de primer y segundo orden, tiras cómicas y baterías WAIS y Luria-DNA. RESULTADOS: Entre los 3 grupos de pacientes únicamente se encuentran diferencias estadísticamente significativas en la realización de viñetas de segundo orden. CONCLUSIONES: Los resultados apuntan hacia la relación entre el déficit en la teoría de la mente y otros déficit neuropsicológicos, aunque hacen falta más estudios para obtener datos sobre las diferencias entre ambos grupos de pacientes (AU)

Esquizofrenia y subjetividad / Schizophrenia and subjectivity

Existe actualmente cierto interés por las denominadas en la esquizofrenia. A lo largo de la historia de esta patología estos fenómenos han tomado forma a través de conceptos como despersonalización-desrealización, automatismo mental, trastornos del yo y autismo. Los autores se proponen revisar dichos síndromes y su asentamiento en el paradigma de la subjetividad entendida como autoconciencia, así como los límites que dicho paradigma encierra. Se concluye tratando de encuadrar este proceso dentro del asunto más amplio de una psicopatología concebida como técnica de producción de inteligibilidad (AU)

Recently, the group of symptoms known as of schizophrenia has raised a grouping interest. These phenomena have been shaped through concepts like depersonalization-derealization, mental automatism, disorders of the self and autism. The authors propose to review these syndromes, as well as their relationship with subjectivity understood as consciousness of the self (or self-awareness) and the shortcomings due to such a relationship. To finish, we will provide some hints into psychopathology understood as a technique of production of intelligibility which will hopefully help to provide a better grasp of the process describe above (AU)

[Schizophrenia and subjectivity]. / Esquizofrenia y subjetividad.

Recently, the group of symptoms known as "subjective experiences" of schizophrenia has raised a growing interest. These phenomena have been shaped through concepts like depersonalization-derealization, mental automatism, disorders of the self and autism. The authors propose to review these syndromes, as well as their relationship with subjectivity understood as consciousness of the self (or self-awareness) and the shortcomings due to such a relationship. To finish, we will provide some hints into psychopathology understood as a technique of production of intelligibility which will hopefully help to provide a better grasp of the process described above.

[Review on the study of the theory of the mind in pervasive development disorders and schizophrenia]. / Revisión sobre el estudio de la "teoría de la mente" en trastornos generalizados del desarrollo y esquizofrenia.

The theory of mind (ToM) is a new concept which could be defined as the ability to make inferences on the intentions of others. This capacity has been used to explain childhood autism symptoms and recently an attempt has been made to refer it to schizophrenia. The authors aim to review the theory of mind concept, the different questions that could appear in neurocognitive sciences and the utilities that this hypothetical model has been given in the clinical practice. The authors also consider the contributions and restrictions that its use has in the field of pervasive developmental disorders and schizophrenia.

Revisión sobre el estudio de la "teoría de la mente" en trastornos generalizados del desarrollo y esquizofrenia / Review on the study of the theory of the mind in pervasive development disorders and schizophrenia

La teoría de la mente es un concepto de corta vida que se define como la habilidad de entender las intenciones de los otros. Esta capacidad ha sido empleada para dar cuenta del autismo infantil y recientemente se ha intentado traspasar a la esquizofrenia. El objetivo de los autores es revisar el concepto de la teoría de la mente, el debate que dicho concepto suscita actualmente en el campo de las ciencias cognitivas y las utilidades que a esta capacidad de mentalizar se le han dado en la clínica. Se examinan tanto las aportaciones como las limitaciones que su uso conlleva en el campo de los trastornos generalizados del desarrollo y la esquizofrenia. (AU)

La interacción social en esquizofrenia y trastornos generalizados del desarrollo: del autismo a la teoría de la mente / Social interaction in schizophrenia and pervasive developmental disorders: from autism to theory of mind

La esquizofrenia y los trastornos generalizados del desarrollo se han relacionado de dos maneras diferentes: primero a través del concepto de autismo y ahora a través del concepto de teoría de la mente. En este artículo se exponen las razones que explican esta relación. Los autores muestran los límites de la psicopatología para dar cuenta de las semejanzas y las diferencias existentes entre ambos. Como conclusión se propone detenerse en el hecho de que se puede diferenciar a estos pacientes a pesar de su parecido, por lo que habrá que prestar atención al procedimiento por el que asignamos el diagnóstico de esquizofrenia o trastornos generalizados del desarrollo (AU)